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Biomedical subjects

G M Smith

Publications and source records attributed to G M Smith.

At least 181 records · Page 10Linked to original sources
PubMed1986

Changing role of forebrain astrocytes during development, regenerative failure, and induced regeneration upon transplantation.

When the cerebral midline is lesioned in the embryo or neonate, the would-be callosal axons form neuromas. We have shown that an untreated Millipore implant inserted between the neuromas in young acallosal animals can support the migration of immature astrocytes that, in turn, support the de novo growth of commissural axons between the hemispheres. Since callosal neuromas persist into adulthood, we asked whether a critical period exists after which reactive glia no longer promote axon growth. We found that a critical period does exist and have documented a variety of changes in reactive gliosis that, in part, may lead to the axon growth-refractory state. In acallosal mouse postnates given untreated implants on or prior to day 8, glial fibrillary acidic protein (GFAP)+, stellate-shaped astrocytes migrated and attached to the implant by inserting foot processes into the pores of the filter. This form of gliotic response established an axon growth-promoting substratum within 24-48 hours after implantation. During this critical stage there was no evidence of scar formation or necrosis at or around the implant surface. However, when acallosal mice were implanted on or later than postnatal day 14, extensive tissue degeneration occurred, and a mixed population of astrocytes and fibroblasts invaded the surface of the filter, producing a dense scar. Reactive cells within the scar did not promote axonal outgrowth. To determine whether glia from neonates can influence the host environment and/or induce axonal regeneration in acallosal animals after the critical period, we harvested immature astrocytes on Millipore from critical-period mouse forebrains and transplanted the glia-coated prostheses into the brains of post-critical-period acallosal animals. Such transplants reduced glial scarring in the host, inhibited extensive bleeding and secondary necrosis, and promoted axonal regeneration. Our studies suggest that when controlled with a prosthesis, gliosis during the critical period is a beneficial process that can promote the reconstruction of malformed axon pathways; that in older animals a variety of changes in reactive glia and the extracellular matrix may work together to hinder axon regeneration after the critical period; and that axonal regeneration in the postcritical CNS may be stimulated by reintroducing an immature glial environment at the lesion site.

Animals↗
PubMed1986

NMR studies of [1-2H]glucose metabolism in Zymomonas mobilis.

In complementary experiments the metabolism of [1-2H]glucose in H2O and of unlabelled glucose in 2H2O by Zymomonas mobilis was examined. The utilization of [1-2H]glucose by Z. mobilis was monitored by high-resolution 2H NMR. The deuterium-labelling pattern and stereochemistry of the ethanols produced from the metabolism of [1-2H]glucose and unlabelled glucose in 2H2O were determined by a combination of 13C and 1H NMR and selective enzyme action. The labelling patterns were explained in terms of enzyme mechanisms and stereospecificity, and metabolite enolization.

Alcohol Dehydrogenase↗
PubMed1986

CV3988 inhibits in vivo platelet aggregation induced by PAF-acether and collagen.

Platelet activating factor (PAF-acether) was shown to cause a fall in the circulating platelet count and blood pressure (BP) in anaesthetised rabbits. CV3988 caused a dose-dependent inhibition of these responses to a low dose of PAF-acether (150 ng X kg-1). CV3988 itself was found to cause a fall in both BP and platelet count in vivo. Collagen (40 micrograms X kg-1) i.v. caused sudden death in rabbits and pretreatment with CV3988 (5 mg X kg-1) caused a 62% inhibition of the platelet count response to collagen without significantly increasing the survival rate. In the rat, collagen (40 micrograms X kg-1) was not lethal and CV3988 caused a dose-dependent inhibition of the fall in platelet count due to collagen, but this action was short-lived. CV3988 also caused agonist actions in the rat. These results show that CV3988 inhibits the effects of PAF-acether in vivo and suggests that PAF-acether may play a role in mediating collagen-induced platelet aggregation in vivo.

Animals↗
PubMed1986

Computer-aided, systematic search of peptide conformations constrained by NMR data.

A computer program has been developed which allows exhaustive exploration of the conformation of medium sized rings (8 to 22-membered). This program provides for inclusion of experimental data from NMR measurements in the form of dihedral angles estimated by the Karplus equation and NOE close contacts. A brief description of the principles used in the program to provide high efficiency are given as is a discussion of the application of this program to a cyclic hexapeptide somatostatin analogue.

Chemical Phenomena↗
PubMed1986

Preliminary evaluation of ciprofloxacin, a new 4-quinolone antibiotic, in the treatment of febrile neutropenic patients.

Twenty-four episodes of fever in neutropenic patients with haematological malignancy were treated with ciprofloxacin. In 13 episodes ciprofloxacin was used after failure of first-line antibiotic therapy, and in 11 episodes because of a history of allergy to the proposed first line antibiotics. Improvement or temporary improvement was seen in 64% of patients with evaluable infection. Fifty per cent of patients with bacteraemia improved. Resistance to ciprofloxacin developed in strains of staphylococci and streptococci, but Gram-negative organisms were generally extremely sensitive to the antibiotic. One patient developed a severe photosensitivity rash but there were no other adverse reactions. Preliminary pharmacokinetic data were obtained following intravenous infusion of 400 mg of ciprofloxacin in five patients. The mean plasma half-life was 3.6 +/- 1.0 h and the mean plasma clearance was 8.42 +/- 2.5 ml/min/kg.

Adult↗
PubMed1986

Single-dose antibiotic prophylaxis of abdominal surgical wound infection: a trial of preoperative latamoxef against peroperative tetracycline lavage.

A randomized controlled clinical trial was undertaken in 542 consecutive emergency and elective abdominal operations, with one group of patients receiving tetracycline peritoneal and wound lavage and the other a single intravenous injection of 1 g latamoxef at induction of anaesthesia. Seventy-five patients were withdrawn because no potentially contaminated hollow viscus was opened, and a further 36 because they could not be assessed for wound infection. Of the remaining 431 patients, 212 received latamoxef resulting in 5 major and 8 minor wound infections in hospital; another 4 minor infections occurred at home (total incidence 8.0%). In the tetracycline group (n = 219) there were 7 major and 19 minor wound infections in hospital and 10 minor infections later (total incidence 16.4%). This is significantly higher than the rate with latamoxef (P = 0.012). Monitoring of operative and postoperative bleeding revealed no evidence (except in one doubtful case) of excessive bleeding associated with the use of a single dose of latamoxef. It is concluded that single-dose preoperative latamoxef is more effective than peroperative tetracycline lavage for the prevention of wound infections after potentially contaminated abdominal operations.

Abdominal Muscles↗
PubMed1985

13C NMR studies of butyric fermentation in Clostridium kluyveri.

The fermentation of 13C-labeled ethanol and acetate into butyrate and caproate by Clostridium kluyveri has been studied by using 13C NMR. The pathway involves the conversion of both ethanol and acetate into acetyl coenzymes A, two of which condense to form CoA-linked precursors of butyrate. If butyryl-CoA is involved in the condensation, caproate is the ultimate product. ATP is produced from acetyl-CoA via the reactions catalyzed by phosphotransacetylase and acetate kinase with acetate, a required carbon source, as a co-product. In spectra of whole cells incubated with the labeled carbon sources, label from ethanol appears rapidly in acetate, which then reaches a lower, steady-state concentration due to its re-entry into the pathway. The rapid initial production of acetate indicates equally rapid production of ATP. Label from acetate appears in ethanol only if ethanol is already present, indicating that this process is one of isotopic equilibration rather than net synthesis of ethanol from acetate. The ratio of butyrate to caproate produced depends strongly on the initial ratio of ethanol to acetate in the medium. The relative rates of utilization of ethanol and acetate vary as the fermentation proceeds. 13C-13C coupling in the butyrate and caproate produced from [1-13C]ethanol and [2-13C]acetate can be used to determine if the acetyl-CoA molecules arising from ethanol and acetate enter the same pool or if they remain separated. The data are consistent with random mixing of the acetyl-CoA produced from the two carbon sources.

Acetates↗
PubMed1985

The involvement of platelets and the coronary vasculature in collagen-induced sudden death in rabbits.

The mechanism of collagen-induced sudden death in rabbits was studied by measuring blood pressure (BP), heart rate, ECG, the continuous platelet count and the plasma levels of thromboxane B2 (TXB2) and 6-keto prostaglandin F1a (6-keto PGF1a). Death was preceded by myocardial ischaemia and a sharp fall in BP which occurred before any fall in platelet count was observed. The calcium entry blockers (CEBS), verapamil, nifedipine and PY 108-068 protected the rabbits from sudden death without any significant effect on the decrease in the platelet count or increase in plasma TXB2 levels. 6-keto PGF1a could not be detected in any plasma samples. Indomethacin and tri-sodium citrate also protected the rabbits but significantly reduced the fall in platelet count and plasma TXB2. In vitro studies on isolated aortae indicated that verapamil non-specifically inhibited vasoconstriction induced by KCl, adrenaline and U46619 (a thromboxane agonist). It is concluded that CEBS physiologically antagonize the vasoconstricting actions of platelet-derived substances and that it is coronary vasoconstriction that is primarily the cause of death.

Animals↗
PubMed1985

Isolation of substances with vascular permeability-increasing activity from the skin of the plaice (Pleuronectes platessa L.).

A methanolic extract of plaice skin, from which lipids had been removed, was chromatographed on alumina, eluted with decreasing concentrations of ethanol. Only the 60% ethanol fraction exhibited smooth muscle activity, with bradykinin-like properties. The 20% ethanol fraction increased vascular permeability in rat skin, as measured by dye-leakage. This was not due to the degranulation of mast cells. Intradermal injection of either fraction into the plaice caused localized erythema.

Animals↗
PubMed1985

Effects of doxylamine and acetaminophen on postoperative sleep.

The separate and combined effects of doxylamine succinate (25 mg) and acetaminophen (1 gm) on sleep were studied by interview procedures and information from medical records of 2,931 postoperative patients. The sample contained 1,617 patients with mild or moderate pain and 1,314 who were free of pain. Each received either doxylamine alone (S), acetaminophen alone (A), a combination of both drugs (C), or placebo (P). Drug treatment was double blind and randomized separately for the pain and pain-free subsamples. Twelve measures of sleep were determined. C was more beneficial than S or A, and S and A were each superior to P. For all 12 sleep measures, the effect of the combination (C - P) approximated or exceeded the sum of the two separate effects (S - P) + (A - P). The presence of either drug tended to enhance the sleep benefit of the other. The sedative and analgesic benefits to sleep were at least additive, and some outcome measures suggested synergism. In the total sample, the contributions of sedative and analgesic similar. Among patients with pain, contributions of the analgesic surpassed those of the sedative. For patients free of pain, the sedative was better, but even pain-free patients had enhanced sleep after the analgesic. The analgesic, but not the sedative, reduced pain; the analgesic induced the feeling of being well rested and not tired; the sedative induced a feeling of being drugged. Nondrug variables (e.g., pain, sex, age, and sleep expectations) influenced sleep outcome at least as much as drugs, but randomization and the large sample prevented those extraneous variables from biasing drug comparisons.

Acetaminophen↗
PubMed1985

Multiply resistant Salmonella typhimurium septicaemia in an immunocompromised patient successfully treated with ciprofloxacin.

A patient with acute lymphoblastic leukaemia developed a septicaemia due to a multiply resistant strain of Salmonella typhimurium probably contracted in Pakistan. This was associated with splenic abscesses and proved resistant to treatment with a succession of beta-lactam antibiotics--ceftazidime, imipenem, and mecillinam despite in-vitro sensitivity. The infection resolved completely with ciprofloxacin therapy--a new 4-quinolone antibiotic which may have an important role in the treatment of systemic salmonella infections.

Adult↗
PubMed1985

A comparative study of the involvement of the prostaglandin H2/thromboxane A2 pathway in intravascular platelet aggregation in guinea-pigs and rats.

The effects of indomethacin, dazoxiben and EPO45 on collagen-induced platelet aggregation in vivo were studied in guinea-pigs and rats to determine the involvement of the prostaglandin endoperoxide/thromboxane A2 pathway in the aggregatory response. Indomethacin and EPO45 (a thromboxane receptor antagonist) partially inhibited platelet aggregation in rats. It was concluded that only one third of the aggregatory response to collagen was mediated by the products of cyclo-oxygenase conversion of arachidonic acid. In rats, dazoxiben was inactive although the conversion of the prostaglandin endoperoxides to thromboxane A2 was inhibited (measured as thromboxane B2). 6-keto PGF1 alpha was detected in plasma after collagen was injected into dazoxiben-treated rats. In this species therefore, the endoperoxides have significant aggregatory activity whilst the apparent increase in the level of prostacyclin was not sufficient to have any anti-aggregatory effect. All three drugs were active in the guinea-pig. About 60% of the aggregatory response to collagen was due to the products of the cyclo-oxygenase pathway, the main mediator being thromboxane A2. In guinea-pigs, dazoxiben also elevated 6-keto PGF1 alpha in the plasma after an injection of collagen. However, this apparent increase in prostacyclin production did not contribute to the anti-aggregatory effect.

6-Ketoprostaglandin F1 alpha↗
PubMed1985

The Collaborative Drawing Technique.

In recent years more and more attention has been focused on the family as the unit of treatment. With this expanded focus, innovations in projective testing are desired to provide information that is meaningful for the treatment process. The Collaborative Drawing Technique represents an effort to meet this need through a projective device which yields information about the functioning of the individual within the context of his family. The CDT was designed to be easily and quickly administered with a minimum of required materials and still give information which can guide the treatment process. To date, the technique has been used primarily as a part of an initial diagnostic interview with families presenting for therapeutic treatment. Research and development are obviously needed in the instrument and several efforts are underway at present.

Adolescent↗
PubMed1984

The structure of a novel polysaccharide isolated from Zymomonas mobilis determined by nuclear magnetic resonance spectroscopy.

A novel polysaccharide has been observed in vivo by 13C nuclear magnetic resonance (NMR) spectroscopy of the gram-negative bacterium, Zymomonas mobilis. The polysaccharide, which was not removed from the Z. mobilis cell by washing with 0.86% saline, was extracted by mild acid treatment. The structure was elucidated by a combination of NMR techniques, including proton and proton-carbon two-dimensional methods. The structure was determined to be -alpha-fructofuranosyl-(2-1)-beta-fructofuranosyl-(2-6)-. The polysaccharide is unlike levan, a beta-(2-6)-fructose polymer which is produced by many bacteria, including Z.mobilis, when grown on sucrose. The polysaccharide isolated here is produced by cells cultured on glucose, fructose or sucrose.

Cell Fractionation↗
PubMed1984

The effect of arachidonic acid metabolism on intravascular platelet aggregation in rats.

The effects of BW755C, benoxaprofen, indomethacin and piroxicam were studied on intravascular platelet aggregation using continuous platelet counting. Plasma levels of thromboxane B2 (TxB2) and 6-keto prostaglandin F1 (6-keto PGF1 alpha) were measured by radioimmunoassay. BW755C, a dual inhibitor of arachidonic acid metabolism, potentiated or inhibited aggregation depending on dose. BW755C increased TxB2 and 6-keto PGF1 alpha plasma levels at low doses. At higher doses BW755C inhibited aggregation and reduced TxB2 plasma levels. At 16 mg/kg BW755C, 6-keto PGF1 alpha was detected. Benoxaprofen also potentiated collagen-induced aggregation. 8 mg/kg indomethacin was shown to have a short lasting increased inhibitory action on collagen-induced aggregation when compared with the more specific cyclooxygenase inhibitor, piroxicam. 6-keto PGF1 alpha was detected in plasma from rats treated with indomethacin and piroxicam. The results obtained using low doses of BW755C suggest that the lipoxygenase pathway is involved in platelet aggregation. Interpretation of the results obtained using higher doses of drugs also suggests this involvement though some nonspecific actions of the drugs must be taken into consideration. Further work is required to detail the role of lipoxygenase products in collagen-induced intravascular platelet aggregation.

4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyraz↗